U.S. patent number 5,094,961 [Application Number 07/626,931] was granted by the patent office on 1992-03-10 for aspiration method for hematology analyzing apparatus.
This patent grant is currently assigned to Coulter Corporation. Invention is credited to Roberto del Valle, Santos E. Vargas, Stuart D. Wills.
United States Patent |
5,094,961 |
del Valle , et al. |
March 10, 1992 |
Aspiration method for hematology analyzing apparatus
Abstract
For use in automated or semi-automated hematology analysis
apparatus, a method of introducing a volume of blood from a source
thereof along a conduit leading to a sampling, metering and
transfer valve assembly of the apparatus comprising the steps of
drawing a predetermined volume of blood sample from the source,
causing the drawn blood sample to travel along the conduit toward
the valve assembly, providing detectors adjacent the inlet and
outlet of the valve assembly and using vacuum to position the drawn
blood sample so that it passes through the valve assembly and is
disposed in metering condition within the valve assembly, the
positioning being responsive to signals provided by the
detectors.
Inventors: |
del Valle; Roberto (Miami,
FL), Vargas; Santos E. (Miami, FL), Wills; Stuart D.
(Cooper City, FL) |
Assignee: |
Coulter Corporation (Hialeah,
FL)
|
Family
ID: |
24512449 |
Appl.
No.: |
07/626,931 |
Filed: |
December 13, 1990 |
Current U.S.
Class: |
436/180; 422/510;
436/174 |
Current CPC
Class: |
G01N
35/1097 (20130101); G01N 33/48 (20130101); G01N
35/08 (20130101); Y10T 436/2575 (20150115); Y10T
436/25 (20150115) |
Current International
Class: |
G01N
33/483 (20060101); G01N 1/00 (20060101); G01N
33/48 (20060101); G01N 35/08 (20060101); G01N
35/10 (20060101); G01N 001/10 () |
Field of
Search: |
;436/180,174 ;422/100
;73/864.83,864.84 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Lacey; David L.
Assistant Examiner: Daley; Thomas E.
Attorney, Agent or Firm: Fox; Sidney N. Hibnick; Gerald
R.
Claims
We claim:
1. A method of introducing a whole blood sample from a source
thereof into a blood analyzing system which includes an aspirator
probe; a blood sampling, metering and transfer valve assembly
operating between a loading condition and a delivery condition;
said valve assembly having a sample inlet port, a sample outlet
port and an internal continuous passage therebetween and, in the
loading condition, defining a continuous sample flow path
therebetween extending from the inlet port to the outlet port
thereof; said valve assembly capable of being operated to assume
the delivery condition from the loading condition thereby
segmenting a body of blood sample into at least one precise volume
aliquot portion thereof for delivery to the blood analyzing system;
small bore conduit means coupled between the aspirator probe and
the inlet port and to the outlet port leading downstream therefrom;
aspirator pump means for drawing the blood sample into the probe,
the blood sample having leading and trailing ends; a source of
vacuum and detector means arranged proximate to said conduit means
at least at a first location downstream of but adjacent the outlet
port of the valve assembly for monitoring the passage of fluid
along the conduit means and sensing the arrival of the leading end
of the blood sample at the first location; the method comprising
the steps of drawing a predetermined volume of a blood sample as a
unit into the aspirator probe; causing the blood sample unit to
travel along the conduit means; stopping the aspirator pump means;
using vacuum from said source continue the travel of the blood
sample unit; detecting the arrival of the leading end of the blood
sample unit at the first location by said detecting means; stopping
the travel of the blood sample unit at the first location;
operating the valve assembly to change the condition thereof from
the loading condition to the delivery condition whereby to segment
the blood sample unit into aliquots of a predetermined volume and
deliver an aliquot to a mixing and testing location of the blood
analyzing system; returning the valve assembly to the loading
condition; and thereafter resuming the travel of any remainent
portion of the blood sample unit.
2. The method as claimed in claim 1 in which said detector means
comprise at least one optical detector.
3. The method as claimed in claim 1 in which the detector means
comprise first and second detectors, the first detector arranged
proximate the conduit at said first location and the second
detector arranged proximate the conduit means at a second location
adjacent the inlet port of the valve assembly so as to detect the
arrival of the leading end of the blood sample unit at said second
location and generate a signal; applying said vacuum to said
conduit means in response to said signal causing the blood sample
unit to continue its travel along said conduit means and pass
through the valve assembly; said detector means comprise optical
detectors which stop the travel of said blood sample unit when the
signals from said optical detectors indicate the presence of the
trailing end of said blood sample unit at the second location and
subsequently the arrival of the leading end of the blood sample
unit at the first location.
4. The method as claimed in any one of claims 1, 2 or 3 further
including the step of introducing an air bubble at the leading end
of the blood sample unit during the initiation of the drawing
thereof from said source and the air bubble is detected by the
detector means.
5. The method as claimed in any one of claims 1, 2 or 3 further
including the step of initially filling the aspirator probe, the
conduit means and the continuous flow path when the valve assembly
is in the loading condition with a pilot fluid before drawing the
sample unit into the aspirator probe to define an interface between
the leading end of the blood sample unit and the pilot fluid, the
interface being detected by the detector means.
6. The method as claimed in any one of claims 1, 2 or 3 in which
the drawing step is carried out by use of a single stroke diaphragm
pump.
7. The method as claimed in any one of claims 1, 2 or 3 wherein the
aspirator probe comprises a piercing needle, the sample source
being a sealed container; piercing the sealed container with the
piercing needle and employing a single stroke diaphragm pump so as
to draw the blood sample unit into the piercing needle.
8. A method for introducing a whole blood sample from a source
thereof into a blood analyzing system of the type which includes
aspirator probe means, a blood sampling, metering and transfer
valve assembly having a sample inlet and a sample outlet, conduit
means coupled between the sample inlet and the aspirator probe
means and to the sample outlet, an internal passage within the
valve assembly constructed so as to define a flow path for a
continuous blood sample unit, the valve assembly operating between
a loading condition and a delivery condition, the flow path being
defined when the valve assembly is in the loading condition, the
valve assembly being operated to assume the delivery condition
thereby segmenting the blood sample unit to define a precise volume
aliquot thereof and delivery of said aliquot to an exterior
location within the blood analyzing system for mixing and testing,
an aspirator pump capable of drawing the blood sample unit of
predetermined volume into the aspirator probe means, a source of
less than atmospheric fluid pressure and detector means including
first and second detectors positioned adjacent the valve assembly
for monitoring the passage of liquid through the conduit means and
flow path and generating a signal in response thereto and flow
control means; said method comprising the steps of:
positioning the first detector proximate the conduit means at a
first location adjacent the sample inlet;
employing the aspirator pump to draw a predetermined volume blood
sample unit into the aspirator probe means and conduit means
thereby creating a blood sample unit with leading and trailing
ends;
sensing the arrival of the leading end of the blood sample unit at
the first location by said first detector and generating a signal
in response thereto;
stopping the travel of the blood sample unit in response to the
signal from the first detector when the leading end thereof is
sensed;
stopping the drawing of the blood sample unit and applying less
than atmospheric fluid pressure from said source to cause the blood
sample unit to continue to travel along the conduit means and pass
through the inlet of the valve assembly along the sample flow
path;
continuing the application of less than atmospheric fluid pressure
to effect continued travel of the blood sample unit through the
outlet of the valve assembly to a second location downstream
thereof;
positioning the second detector proximate the conduit means at a
second location downstream of the outlet of the valve assembly but
adjacent thereto;
sensing the arrival of the leading end of the blood sample unit at
said second location by said second detector and generating a
signal in response thereto;
stopping the continued travel of said blood sample unit at said
second location by discontinuing the application of the less than
atmospheric fluid pressure to the conduit means in responsive to
said signal provided by said second detector;
operating the valve assembly to change the condition thereof from
the loading condition to the delivery condition when the travel of
the blood sample unit is stopped whereby to segment the blood
sample unit within the valve assembly so as to create an aliquot
portion of precise volume of said blood sample unit and deliver the
said aliquot portion to a mixing and testing location within the
blood analyzing system; and,
thereafter, returning the valve assembly to the loading
condition.
9. The method as claimed in claim 8 in which the entire flow path,
including the aspirator probe means, the conduit means and the
valve assembly, which includes the internal sample passage thereof,
is filled with a pilot fluid prior to drawing of the blood sample
unit into the aspirator probe means whereby to define an interface
between the leading end of the drawn blood sample unit and said
pilot fluid .
10. The method as claimed in claim 8 including a source of diluent;
and the step of reversing the flow within the conduit means and
associated continuous flow path, after the valve assembly has been
returned to the loading condition and prior to drawing of a
followed blood sample unit, by introducing the diluent from said
source to the conduit means downstream of the outlet whereby to
backwash the entire flow path including the aspiration probe
means.
11. The method as claimed in any one of claims 1, 2 or 3 in which
the conduit means are constructed from a flexible fluoroethylene
derivative material non-adherent to blood and the flow control
means comprise plural pinch valves.
12. In a method for introducing a volume of blood from a source
thereof via sample receptor means to a blood sampling, metering and
transfer valve assembly of a blood analyzing system in which the
valve assembly is constructed so as to operate between a loading
condition and a delivery condition and has sample inlet and outlet
ports and a conduit portion constructed of a non-blood adhering
material and coupled to the sample receptor means and the inlet and
outlet ports thereby defining a continuous sample flow path from
the sample receptor means through the valve assembly and downstream
of the outlet port; the method including the steps of drawing a
predetermined volume of blood sample as a unit from the source
thereof into the sample receptor means, defining a sample body unit
of a blood sample along said conduit portion coupled to the inlet
port of the valve assembly, the body unit of blood sample having
leading and trailing ends, establishing a source of reduced
pressure and coupling the source of reduced pressure to the valve
assembly via the conduit portion coupled to the outlet port of the
valve assembly; the improvement further comprising the additional
steps of establishing a continuous body of pilot fluid along the
flow path from the sample source including the sample receptor
means, the conduit portion, the inlet and outlet ports of the valve
assembly and the internal passage constructed so as to individually
link said ports at a time prior to the drawing of the body unit of
blood sample for creating an interface between the body of pilot
fluid and the body unit of blood sample after drawing of the body
unit of blood sample; sensing the leading end of the body unit of
blood sample at a first location along the conduit portion short of
the inlet port of the valve assembly and providing a first signal,
stopping the travel of the body unit of blood sample in response to
said first signal before the body unit of blood sample reaches the
inlet port, applying reduced pressure from said source to the
conduit coupled to the outlet port of the valve assembly to
continue the travel of the body unit of blood sample through the
valve assembly along the internal passage therein through the
outlet port and to a second location downstream thereof, sensing
the arrival of the leading end of the body unit of blood sample at
said second location and providing a second signal, sensing the
presence of the trailing end of the body unit of blood sample at
said first location, and subsequently stopping the travel of the
body unit of blood sample at said second location only if the
presence of the trailing end of the body unit of blood sample is
indicated when the second signal is provided.
13. The method as claimed in claim 12 further including the steps
of operating the valve assembly to segment the body unit of blood
sample within the valve assembly to define an aliquot portion
thereof and deliver said aliquot portion to a predetermined
location within the blood analyzing system at a time subsequent to
the provision of the second signal and the stopping of the travel
of said body unit of blood sample in response thereto, and,
thereafter, returning the valve assembly to its loading condition
and directing the remaining blood of the body unit of blood sample
to a predetermined location at a time subsequent to the completion
of the segmentation and the delivery of the aliquot portion.
14. The method as claimed in claims 12 or 13 in which an air bubble
is formed at the interface between the body unit of blood sample
and the pilot fluid to denote said interface, the air bubble being
sensed to generate the respective signals.
15. The method as claimed in claim 12 or 13 further including the
step of pinching the conduit just prior to drawing of the blood
whereby an air bubble is introduced at the leading end of the body
unit of blood sample to denote the interface between the body unit
of blood sample and the pilot fluid.
16. The method as claimed in claim 13 further comprising the step
of backflushing the flow path along the conduit portions and valve
assembly using pressurized fluid directed in a reverse direction
relative the flow of blood during the step of drawing the blood,
said backflushing being undertaken subsequent to said returning of
the valve assembly to its loading condition.
17. The method as claimed in claims 12 or 13 in which the pilot
fluid is an isotonic diluent.
18. The method as claimed in claims 12 or 13 wherein the volume
drawn is only slightly greater than the minimum volume required
within the valve assembly for disposition thereof for the delivery
condition.
19. The method as claimed in claims 12 or 13 in which the flow
control means comprise pinch valves.
20. The method as claimed in claims 13 or 14 in which the flow
control means comprise solenoid operated pinch valves.
21. A method of introducing a predetermined volume unit of a sample
from a source thereof into a metering and transfer valve assembly
of an analyzing system in which there is a source of reduced
pressure, an aspirator probe, the metering and transfer valve
assembly constructed so as to operate between a loading condition
and a delivery condition and having a sample inlet, port a sample
outlet port, a continuous internal passage defined within the valve
assembly between the sample inlet and outlet ports during the
loading condition and a flexible conduit means constructed so as to
define with said internal passage a continuous flow path from the
aspirator probe to and through the valve assembly at least
downstream of the outlet port', the conduit means including a first
flexible conduit constructed so as to link the aspirator probe to
the inlet port and coupled thereto and a second flexible conduit
coupled to the outlet port', signal generating detector means
arranged proximate to the first and second conduits at first and
second locations respectively adjacent the inlet and outlet ports
so as to monitor the passage of fluid along the flow path;
aspirator pump means coupled to the second conduit for drawing a
predetermined volume unit of sample from the source thereof into
the aspirator probe and the first conduit, the volume unit having a
leading end and a trailing end; flow control means responding to
the detector signals and operating upon the flow of the sample unit
along the flow path; the method comprising the steps of:
causing the aspirator pump means to draw a predetermined volume of
sample as a unit into the aspiration probe and along the flow
path;
detecting from a first detector of said detecting means the arrival
of the leading end of said sample unit at a first location short of
the inlet port and generating a first signal in response
thereto;
stopping the aspirator pump means;
stopping the flow of the said volume unit at said first location
along the flow path in response to said first signal from said
first detector;
applying reduced pressure to the second conduit to resume the flow
of said volume unit along the flow path and through the inlet port,
the internal passage and the outlet port of the valve assembly and
into the second conduit downstream of the outlet port;
detecting from a second detector of said detecting means the
arrival of the leading end of said volume unit at the second
location and generating a second signal in response thereto;
and,
stopping the flow of said volume unit at the second location in
response to said second signal only if the trailing end of said
volume unit is sensed at the first detector indicating its presence
at the first location.
22. The method according to claim 21 in which said first and second
locations are adjacent the respective inlet port and outlet
port.
23. The method according to claim 21 and the additional step
of:
initially filling the continuous flow path with a pilot fluid
before drawing the unit of sample into the aspirator probe whereby
creating a detectable interface between the pilot fluid and the
leading end of said sample unit.
24. The method according to claim 21 in which a meniscus is
permitted to be present at the entry to the aspirator probe prior
to drawing of the predetermined volume unit of sample thereinto so
that an air bubble is drawn into the aspirator probe at the leading
end of said volume unit when said volume unit is drawn into the
aspirator probe, the air bubble denoting the interface.
25. The method according to any one of claims 21, 22 or 23 in which
the flow control means comprise pinch valves.
26. The method according to any one of claims any one of claims 21,
22 or 23 in which the volume of the sample unit drawn into the
aspirator probe is only slightly greater than the minimum volume
required to fill the path defined by the inlet port, the internal
passage and the outlet port of the valve assembly.
27. The method according to any one of claims 21, 22 or 23 in which
only reduced pressure is employed to effect flow of said volume
unit subsequent to the stopping of the travel of said volume unit
at the first location.
28. A method of introducing a predetermined volume unit of whole
blood sample from a source thereof into a blood analyzing system
which includes a source of vacuum, a metering and transfer valve
assembly constructed so as to operate between a loading and a
delivery condition and having sample inlet and sample outlet ports,
a continuous internal passage between the inlet and outlet ports
and conduit means constructed so as to define with said internal
passage during the loading condition a continuous flow path from an
aspirator probe to and through the valve assembly at least
downstream of the outlet port; the conduit means including a first
conduit constructed so as to link the aspirator probe to the inlet
port and a second conduit coupled to the outlet port; signal
generating detector means positioned adjacent to the inlet and
outlet ports for monitoring the passage of fluid along the flow
path; aspirator pump means coupled to the second conduit for
drawing a predetermined volume unit of sample from the source
thereof into the aspirator probe and the flow path along the first
conduit, the volume unit having a leading end and a trailing end;
flow control means responding to the detector signals and operating
upon the flow of the volume unit along the flow path; the method
comprising the steps of:
employing the aspirator pump means to draw a predetermined volume
unit of the blood sample into the aspiration probe and along the
flow path;
stopping the aspirator pump means upon completion of the drawing of
the predetermined volume of the blood sample unit;
continuing the flow of the blood sample unit along the flow
path;
detecting by said detecting means arrival of the leading end of the
blood sample unit at the first location and generating a signal in
response thereto;
stopping the flow of the blood sample unit at the first location in
response to said signal;
applying a vacuum from said source to the second conduit to
continue the flow of the blood sample unit along the flow path
through the inlet port, the internal passageway, the outlet port
and second conduit;
sensing the position of the blood sample unit relative to the first
and second locations and generating a second signal when the
leading end of the blood sample unit reaches the second location
and the trailing end of the blood sample unit is sensed as present
at the first location;
stopping the flow of the blood sample unit at the second location
in response to said second signal;
operating the valve assembly to segment the blood sample unit
within the valve assembly whereby to isolate an aliquot of precise
volume of said blood sample unit within the valve assembly;
delivering the isolated aliquot from said valve assembly to a
predetermined location within the blood analyzing system; and
returning the valve assembly to its loading condition.
29. The method according to claim 28 and the additional step
of:
initially filling the continuous flow path with a pilot fluid
before drawing the blood sample unit into the aspirator probe and
creating an interface between the leading end of the blood sample
unit and the pilot fluid when the blood sample unit is drawn.
30. The method according to claims 28 or 29 further including the
steps of applying said vacuum from the vacuum source to the flow
path diverting any remainent sample unit after the delivery to a
waste receptacle subsequent to return of the valve assembly to its
loading condition.
31. The method according to claims 28 or 29 wherein the pump means
comprise a single stroke pump operative to draw the predetermined
volume to define the blood sample unit into the aspirator probe
whereby limiting the volume drawn to the quantity required to fill
the flow path between the entry to the sample flow path and the
outlet of the sample flow path of the valve assembly.
32. The method according to claims 28 or 29 in which the conduit
means are constructed from a flexible material and the flow control
means are pinch valves positioned along the conduit means, the
pinch valves being operated selectively to permit and to stop
liquid flow along the flow path defined by the conduit means.
Description
CROSS REFERENCE TO RELATED PATENTS
The subject matter of each of the following patents is hereby
incorporated by reference hereto as a part of this application for
the disclosure contained therein:
U.S. Pat. No. 4,609,017 granted on Sept. 2, 1986 to Wallace H.
Coulter et al. for Method and Apparatus for Transporting Carriers
of Sealed Sample Tubes and Mixing the Samples;
U.S. Pat. No. 4,752,690 granted on June 21, 1988 to Bobby D. James
for Method and Apparatus for Detecting Incongruities, Such As Air
Bubbles, in Fluid Material.
FIELD OF THE INVENTION
This invention relates generally to hematology analyzing apparatus
and more particularly provides an improved method for introducing
whole blood samples to such apparatus for analysis.
BACKGROUND OF THE INVENTION
Automated and semi-automated hematology analysis apparatus of the
type employed for measuring a plurality of parameters of a whole
blood sample have been in common use for many years. One of such
systems is the subject of U.S. Pat. No. 3,549,994 and in using such
systems, means have been provided for introducing whole blood
samples into the system manually via an open-mouthed sample
container which is held up to an aspirating tube or probe from
which it is aspirated and thereby directed to a metering, transfer
and delivery valve assembly of the type taught by U.S. Pat. No.
4,445,391. The said type of valve assembly meters the aspirated
sample into precise volume aliquots and delivered with a
predetermined volume of diluent to the testing means provided
within the system.
Although numerous improvements have been made over the years to
systems of the type concerned, for many years the method and means
for introducing sample to the system have remained unchanged. Some
advances have been made in sample handling such as taught in U.S.
Pat. No. 4,609,017 in that sealed sample containers have been
provided and handled by automatic and semiautomatic feed
arrangements using holding racks and piercing needle means to
combine sample mixing and aspiration enabling with a goal to
minimize technician interaction and reducing the sample volume
required. In such apparatus, the piercing needle is coupled by a
fluid conduit line to the metering, transfer and delivery valve
assembly. In some of these systems, the piercing needle means is
required to be physically located within a very short distance from
the valve assembly. In such systems, the aspirated blood volume is
required to be large enough to fill the needle, the connecting
fluid conduit and the valve assembly. This aspirated blood volume,
of course is continuous along such route and hence is much greated
than required to fill the valve assembly.
In respect of systems wherein manual aspiration means are provided,
again the volume of aspirated blood sample is much larger than
necessary to enable the valve assembly to provide the required
aliquot portions. Conservation of sample has been and remains an
important and as yet unrealized goal to the extent theoretically
possible. Even where the sample aspiration probe is directly
secured to the valve assembly, the volume aspirated into the probe
has been far greater than the theoretical minimum, the excess
passing through the valve assembly and to waste. Thus whether the
aspiration station, whether it involves a piercing needle
semi-automatic or automatic mode or a manual aspiration probe mode,
is remote from the valve assembly or closely adjacent the valve
assembly, the resultant aspirated sample volume is greater than
actually required for the determinations sought to be obtained.
Another deterrent to the efficient aspiration of whole blood sample
is the structural complexity required where the aspiration station
and the valve assembly are positioned closely adjacent one another.
If it were possible to obtain minimum volume units of sample at a
location remote from the valve assembly and transport said units to
the valve assembly with preservation of their integrity so that
only the volume required to establish the necessary fluid body for
segmentation within the valve assembly to provide the aliquot
portions is drawn, the volume of blood sample to be aspirated would
be manifestly reduced.
Thus it would be desirous to provide an blood sample aspiration
method which would enable the reduction of the volume of whole
blood sample aspirated to an amount at least close to the
theoretical minimum required to isolate the required aliquot
portions of the sample necessary to obtain the desired parameters
of said sample. Also sought is a method for locating the aspiration
station remote from the valve assembly yet assuring continuity of
sample and maintaining the integrity thereof. Further, another
advantage sought is an inexpensive method to position the body of
blood sample so that it just fills the flow path therefor within
the sampling valve assembly. The method sought by the art to solve
the above problems likewise should improve the ease of cleaning the
aspiration lines from the probe tip through the blood sampling
valve without needing the backflushing conventionally
available.
SUMMARY OF THE INVENTION
The herein describe invention provides a method for introducing a
volume of whole blood sample from a source thereof, either via
piercing needle means or manual probe means, to a blood metering,
transfer and delivery valve assembly, which volume is substantially
equal to substantially the minimum volume required to establish a
segmentable body of said sample within the valve assembly; driving
the drawn volume of blood sample as a unit to and through the valve
assembly to reach a location exterior of the valve assembly yet
adjacent the sample outlet thereof; detecting the arrival of the
leading edge of the drawn sample volume to a first location closely
spaced from the entry port of the valve assembly; detecting the
arrival of said sample volume to a second location closely adjacent
the sample outlet of the valve assembly; and stopping the flow of
said drawn sample volume at said second location to position said
unit volume relative said valve assembly to permit the required
segmentation of said drawn sample unit into aliquot portions
thereof. Provision is made to effect backwash of the remainent
sample volume by flowing diluent or rinse fluid to retrace the
aspiration flow path.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic representation illustrating the aspiration
method according to the invention;
FIG. 2 is a schematic representation illustrating a modification of
the aspiration method according to the invention; and,
FIG. 3 is an elevational sectional view of a detector employed in
practising the aspiration method according to the invention.
DESCRIPTION OF PREFERRED EMBODIMENTS
Briefly, the aspiration method according to the invention herein
consists of aspirating a volume of whole blood sample only
sufficient to fill the interior sample aspiration flow path within
the metering, transfer and delivery valve assembly of the
hematology analyzing system, causing said volume to flow as a unit
along a fluid conduit leading to the sample inlet of the metering,
transfer and delivery valve assembly, through the interior sample
aspiration flow path within the valve assembly and continuing from
the outlet of said flow path through a fluid conduit exterior of
the said valve assembly, there being an interface between the unit
and a pilot fluid, detecting the arrival of the interface at a
first location adjacent the sample inlet of the valve assembly to
generate a first signal, detecting the arrival of the interface at
a second location adjacent the sample outlet of the valve assembly,
stopping the flow of said sample unit, using the first signal to
initate the flow of said sample unit into the inlet port of the
valve assembly, using the second signal to stop the flow of said
sample unit at the second location, positioning the sample unit to
permit operation of the valve assembly to segment the necessary
aliquot portions as required, by operation of said valve assembly
to segment said sample unit as required to obtain the desired
parameters of said blood sample, the aspiration flow continues so
that the interface is detected, the first signal causing the
aspiration to cease and vacuum to continue the flow through the
valve assembly to the second location, the second signal causing
the flow to stop at the second location.
In the preferred embodiment detection of the blood sample unit by
both detectors is required to effect stopping the flow of said
travelling blood sample unit so that it is properly positioned
relative to the metering, transfer and delivery valve assembly. The
valve assembly then is operated to cause the segmentation of the
sample unit to form the necessary sample aliquots. The valve
assembly then is operated to deliver the aliquots with respective
predetermined volumes of diluent, to the testing chambers of the
system. The valve assembly then is operated to place the valve in
backwash condition, whereupon vacuum is applied to direct any
residual blood sample contained in the aspiration flow path through
the fluid conduit and valve assembly to a waste chamber. Reverse
flow of rinse or diluent liquid is initated to backwash said flow
path readying the system for the next sample aspiration.
It is necessary that the fluid conduit be formed of a material to
which the blood is non-adherent, such as for example, Teflon (a
trademark of DuPont Co.), so that the blood does not adhere to the
inner wall of said conduit. The pilot fluid preferably is isotonic
diluent such as manufactured and sold by Coulter Electronics, Inc.
under the registered trademark Isoton.
Referring to FIG. 1 of the drawing, the aspiration station is
represented by the piercing needle 10 which is coupled to the blood
metering, transfer and delivery valve assembly 12 via first and
second small bore flexible conduits 14 and 16 formed of Teflon
material, with a first detector 18 interposed between said
conduits. The piercing needle 10 is arranged to enter the sealed
whole blood container C through the seal thereof. The outlet 10' of
the piercing needle 10 is coupled to the conduit 14, thence to the
input port 20 of the first optical detector 18. The outlet port 22
of the first optical detector 18 is positioned closely adjacent the
sample inlet port 24 of the valve assembly 12 and coupled thereto
by second flexible conduit 16. The sample outlet port 26 of the
valve assembly 12 is coupled to the input port 28 of a second
detector 30 by third flexible conduit 32, also formed of Teflon
material. The outlet port 34 of the second detector 30 is coupled
to fourth flexible conduit 36, in turn coupled through first pinch
valve 40 to the leg 42 of first Y-connection 44, the first pinch
valve 40 being controlled by solenoid 46. The arm 48 of first
Y-connection 44 is coupled, via line 50 through second pinch valve
52 to the arm 54 of the second Y-connection 56, in turn coupled via
leg 58 to the delivery side of first single stroke diaphragm pump
60, said diaphragm pump 60 having a predetermined volume, here 175
microliters. The input 62 of pump 60 is coupled to leg 64 of third
Y-connection 68, the arm 66 of said third Y-connection 68 leading
via third pinch valve 70 to a source S-1 of 30 PSI pressurized
fluid.
Arm 72 of first Y-connection 44 is coupled to leg 74 of the fourth
Y-connection 76. Arm 78 of fourth Y-connection 76 is coupled to arm
80 of the fifth Y-connection 82 through the fifth pinch valve 84.
Fourth pinch valve 76 is controlled by solenoid valve 132. Arm 80
of the fifth Y-connection 82 is coupled via leg 88 of the fifth
Y-connection 82 to the delivery port 90 of the second single stroke
diaphragm pump 92. Arm 94 of the fifth Y-connection 82 is connected
via check valve 96 to a source S-3 of isotonic diluent which serves
as a pilot fluid in the system concerned herein. The second single
stroke diaphragm pump 92 has a capacity of 1 cc. The input port 98
of pump 92 is coupled to the leg 100 and thence to arm 102 through
the sixth pinch valve 110 via line 106 to the source S-1 of 30 PSI
pressurized fluid, said sixth pinch valve 110 also being operated
by solenoid 86.
The arm 114 of fourth Y-connection 76 is coupled to the arm 118 of
seventh Y-connection 120 via line 122 passing through the fourth
pinch valve 126. The fourth pinch valve 132 is controlled by
solenoid valve 132. The leg 128 of seventh-Y connection 120 is
coupled to the vacuum/waste chamber 134 via line 130. The
vacuum/waste chamber 134 is coupled to source S-4 of 5 PSI
pressurized fluid through seventh pinch valve 136 via line 138. The
vacuum/waste chamber 134 is coupled to a vacuum source S-2" through
eighth pinch valve 140 via lines 142 and 142', said eighth pinch
valve 140 being controlled by solenoid 156. The outlet 144 of the
vacuum/waste chamber 134 is coupled to a waste receptacle 146 along
line 148 through ninth pinch valve 152 and line 154. Ninth pinch
valve 152 is operated also by solenoid 86.
The preferred inner diameter of conduits 14, 16, 32 and 36 are
identical, preferably 0.028 inches. In a preferred embodiment, the
length of conduit 14 is 15.5 inches; the length of conduit 16 is
3.25 inches; the length of conduit 32 is 3.00 inches; the length of
conduit 36 is 6.5 inches and the length of conduit 38 is 13.0
inches. The inner diameter of conduit 38 preferably is 0.040
inches, hence larger than the inner diameter of the conduits 14,
16, 32 and 36.
Preferably, the optical detectors 18 and 30 are identical to the
detectors described and claimed in U.S. Pat. No. 4,752,690 of June
21, 1988 incorporated by reference herein. The preferred detectors
18 and 30 provide electrical signals indicative of optical opacity
of the fluid flowing therethrough. The signals thus derived are
compared against a diluent reference level signal to provide a
resulting signal output indicating the presence of the interface of
the flowing blood sample unit. Each said detector is adapted to
detect changes in fluid density, i.e. opacity, of the fluids
flowing therethrough. This requires that the detector units respond
to subtle changes in light level. The detector is constructed to be
free from extraneous surrounding or reflecting light. A rigid block
160 of material (substantially impervious to the passage of light
therethrough) is bored, machined, cast, molded or otherwise formed
to provide a fairly deep, well-like central opening 160' therein
from which two substantially parallel additional lozenge shaped,
receptacle-like openings 162 (only one illustrated) extend
downwardly well into the body of block 160. A vertical wall member
164, separating the two parallel openings 162 is provided as a
result of the casting or drilling operation.
Horizontal through holes 166 are formed through opposite sides of
the block 160 approximately midway between its bottom 168 and top
170 of the openings 162. A second horizontal through hole 172
extends into and through block perpendicular to the holes 166. A
stainless steel tube press-fitted into and through the holes 172
providing a rigid attachment fitting extending from both sides of
the block. Utilizing the manufacturing holes for drill access, a
window 176 is defined of relatively small diameter (0.19 inches)
which is drilled through the central wall member 164 and through
the stainless steel tube 174. A close fitting length of transparent
rigid material 178 is inserted into and through the stainless steel
tube 174 and is secured to it with suitable bonding material.
The light sensing assembly is accuratedly oriented within the block
160 so that the axial centers thereof are aligned with the center
of the window 176 thus assuring that the light will pass through
the window with minimum loss due to the tolerance of the associated
parts of the assembly. The detector 18 senses and causes a signal
to be generated which is transmitted to means for operating the
solenoid controlled pinch valves which in turn control flow of the
blood sample unit along the flow path concerned. For more details
concerning the construction and operation of the detectors 18 and
30, reference is made to U.S. Pat. No. 4,752,690 incorporated by
reference herein.
According to the method of the invention, prior to the initiation
of the aspiration of a whole blood sample, the entire aspiration
system, including the valve assembly 12 and the respective conduits
have been backwashed and filled with the isotonic diluent, the
latter functioning as the pilot fluid during the transport of the
aspirated sample. Now the solenoid 46 is activated, which causes
the pinch valve 40 to operate, to unpinch the line 38 leading to
the leg 42. This creates the air bubble which serves as the
interface for the leading end of the aspirated whole blood sample.
Solenoid 46 also activates pinch valve 52 after the piercing needle
10 passes through the seal of container C to reach the whole blood
sample therein. With the solenoid 46 still activated, both pinch
valve 52 and 70 unpinch. This activates the diaphragm pump 60,
drawing the volume of whole blood sample, referred to as the blood
sample unit, into the flexible conduit 14. The blood sample unit as
it travels along conduit 14 may or need not reach the input port 20
of the first detector 18. However, it will not reach the sample
input port 24 of the sampling, metering and transfer valve 12.
When the air bubble (sample/pilot fluid interface) reaches the
sensing means within the detector 18, a signal is generated and a
command issued from the control means (not shown). The solenoid 70
is deactivated and pinch valves 126 and 140 are activated, with
pinch valve 40 still in the unpinching condition. Vacuum thus is
applied to the conduit lines 38, 36, 32, 16 and 14, causing the
travel of the blood sample unit along said conduits past the first
detector, into the valve assembly (then in loading condition) and
passes through the sample outlet 28 of the valve assembly 12 along
conduit 32 to the detector 30. When the air bubble at the leading
edge of the sample unit is detected by the second detector 30, and
while the first detector still generates the signal indicating that
the length of the sample unit is still within the first detector, a
command is directed to the solenoid 46 to deactivate the pinch
valve 40, whereupon the pinch valve pinches the line 38, 42,
stopping the blood sample unit.
Now the valve assembly 12 is operated to segment the body of blood
sample within the interior loading flow path therein, whereby to
isolate the required aliquot portions thereof. Diluent is fed to
the valve assembly driving the respective aliquot portions with
given volume of diluent respectively to the mixing and testing
baths provided in the analysis system whereby the testing is
performed to provide the desired parameters of said sample. The
pinch valves 40, 126 and 86 are caused to operate to unpinch the
respective lines passing therethrough whereby vacuum is drawn on
the conduit 138 causing the remainent blood sample to be drawn to
the vacuum/waste chamber 134 and, through line 154 to the waste
reservoir (container) 146.
Referring to FIG. 2, the manual mode of the method according to the
herein invention shall be described. The volume of sample required
is reduced compared to the volume required employing the automatic
(piercing needle, etc) mode since the volume needed to fill
conduits 14 and 16 is not required. The sample probe 136 is secured
to the sampling, metering and transfer valve assembly 12 with the
sample outlet thereof coupled to conduit 32. Only a single detector
30 on the outlet side of the valve assembly 12 is required. The
input of the aspiration probe 136, which had been filled with pilot
fluid also has an inwardly arced meniscus so that the air bubble is
created upon entry of the blood sample into the probe 136 when
aspiration is initiated. The said air bubble defines the leading
edge of the body of blood sample as it travels up the probe and
into the valve assembly (which is disposed in the loading condition
thereof).
When the air bubble reaches the sensing means of the detector 30, a
signal is generated and directed to the control means for system
and the pinch valves 52 and 70 operate to pinch the aspiration
lines, also causing the pinch valve 40 to pinch line 38 and stop
the travel of the sample unit. The valve assembly 12 is operated to
segment the sample unit within the valve assembly and thus provide
the necessary aliquot portions. Diluent is introduced to flush the
aliquots, along with the diluent, to the mixing vessels and testing
vessels of the analysis system.
The purpose of the detectors according to the invention is to
position the blood sample unit so that its length is close to the
minimum necessary to provide the number of sample aliquots required
for determining the parameters desired and, further, to control the
flow of the blood sample unit.
It should be noted that the conduits, pinch valves, valve assembly
and probe can be backwashed using the second diaphragm pump to
provide a reverse flow along the aspiration route, subsequent to
the completion of the discharge of the remainent portions of the
sample unit to the waste receptacle 146. One also can wash the
system by drawing diluent (or rinsing liquid) by aspirating same or
using the line 156 to introduce said diluent under the reduced
pressure (5 PSI) unpinching pinch valve 136.
It is clear that one skilled in the art can make changes and/or
modifications to the method of the invention yet remain within the
scope of the invention as claimed hereinafter.
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